1. Field of the Invention
The present invention relates generally to the fields of microbiology, immunology and pathology. More particularly, it concerns the development of human monoclonal antibodies for use in the diagnosis, prevention and therapy of Streptococcus pneumoniae infections.
2. Background of the Invention
Streptococcus pneumoniae is a ubiquitous human pathogen causing a range of clinical infections, such as otitis media, pneumonia, meningitis, and bacteremia. The more serious manifestations are especially virulent in immunocompromised and elderly individuals. Over 90 different S. pneumoniae serotypes have been characterized, each having a different capsular polysaccharide structure. These polysaccharides are immunogenic in adults, and the Pneumovax®23 vaccine consists of a cocktail of 23 of the most common and/or virulent S. pneumoniae strains. The vaccine is recommended for everyone over the age of sixty, as well as all immunocompromised individuals, to ensure seroprotection against these strains.
The serology of the response to Pneumovax®23, as well as the conjugate vaccine Prevnar® (used to immunize children), has been studied in depth with regard to the humoral polyclonal IgG and IgA responses in both sera and saliva (Anttila et al., 1999; Nieminen et al., 1998a; Nieminen et al., 1998b). The memory and antibody secreting cell (ASC) response to these vaccines has also been previously explored on a cellular level with B cell ELISpot assays and flow cytometry Nieminen et al., 1998b; Clutterbuck et al., 2006), and the presence of both responses after vaccination is now well established. However, utilizing ASCs to produce human monoclonal antibodies would provide a novel way to fully elucidate the recall response to pathogen serotypes after vaccination, and even provides a window to explore the evolution of past responses.
Antibodies that cross-react to two or more pneumococcal polysaccharides are present in sera both pre- and post-immunization (Lee et al., 1984; Soininen et al., 2000); however, whether this is due to single antibody specificities that are capable of cross-reacting or rather due to broad polyclonal antibody specificities is not known. Although it has been reported that immunization with Pneumovax®23 in patients with SLE does not induce new auto-specificities (Elkayam et al., 2005), one report has shown that kidney-binding antibodies in a patient with SLE also cross-reacted with pneumococcal polysaccharide (Chowdhry et al., 2005). Thus, it is possible that antibodies produced from B cells in SLE donors may show increased poly-reactivity or auto-reactivity. It is only possible to determine such per-antibody phenomenon by the characterization of human monoclonal antibodies from SLE donors.